Ketones ozonolysis, ozone

We have seen that alkenes can be oxidized to 1,2-diols and that 1,2-diols can be further oxidized to aldehydes and ketones (Sections 20.6 and 20.7, respectively). Alternatively, alkenes can be directly oxidized to aldehydes and ketones by ozone (O3). When an alkene is treated with ozone at low temperatures, the double bond breaks and the carbons that were doubly bonded to each other find themselves doubly bonded to oxygens instead. This oxidation reaction is known as ozonolysis. 

In a similar manner N-(2-ethyl)butylidenepiperidinium hexachlorostannate gives mostly diethyl ketone and only a little of 2-ethylbutanal when a fresh solution is ozonized. If allowed to stand for a period of time, the only product obtained by ozonolysis is 2-ethylbutanal 16). 

Low -molecular-weight ozonides are explosive and are theretore not isolated. Instead, the ozonide is immediately treated with a reducing agent such as zinc metal in acetic acid to convert it to carbonyl compounds. The net result of the ozonolysis/reduction sequence is that the C=C bond is cleaved and oxygen becomes doubly bonded to each of the original alkene carbons. If an alkene with a letrasubstituted double bond is ozonized, two ketone fragments result if an alkene with a trisubstituted double bond is ozonized, one ketone and one aldehyde result and so on. 

To form ketones or aldehydes, a wide variety of oxidizing agents work, including air. The most common/useful oxidants contain chromium or manganese. Ozone, for ozonolysis, is also a useful oxidant to form aldehydes and ketones from alkenes. 

The oxidation of an alkene with ozone followed by treatment with zinc in the presence of acid gives aldehydes and/or ketones. The reaction breaks the carbon-carbon double bond and changes each of carbon atoms of the C=C to a carbonyl group. Figure 10-7 shows an excimple of the ozonolysis of an alkene. 

Synthetic operations involving ozonolysis lead to formation of aldehydes, ketones or carboxylic acids, as shown in Scheme 16, or to various peroxide compounds, as depicted in Scheme 7 (Section V.B.5), depending on the nature of the R to R substituents and the prevalent conditions of reaction no effort is usually made to isolate either type of ozonide, but only the final products. This notwithstanding, intermediates 276 and 278 are prone to qualitative, quantitative and structural analysis. The appearance of a red-brown discoloration during ozonization of an olefin below — 180°C was postulated as due to formation of an olefin-ozone complex, in analogy to the jr-complexes formed with aromatic compounds however, this contention was contested (see also Section V1I.C.2). 

Alkenes can be cleaved by ozone followed by an oxidative or reductive work-up to generate carbonyl compounds. The products obtained from an ozonolysis reaction depend on the reaction conditions. If ozonolysis is followed by the reductive work-up (Z11/H2O), the products obtained are aldehydes and/or ketones. Unsubstituted carbon atoms are oxidized to formaldehyde, mono-substituted carbon atoms to aldehydes, and di-substituted carbon atoms to ketones. 

The ozonolysis of olefins may be analyzed as a sequence of two 1,3-dipolar cycloadditions initial electrophilic attack by ozone 18 to form the first intermediate, which decomposes into a carbonyl compound and a carbonyl oxide 14 followed by nucleophilic 1,3-dipolar addition of the carbonyl ylide 14 to the ketone, yielding the molozonide. 

Ozonolysis allows the cleavage of alkene double bonds by reaction with ozone. Depending on the work up, different products may be isolated reductive work-up gives either alcohols or carbonyl compounds, while oxidative work-up leads to carboxylic acids or ketones. 

A historically important use of the ozonolysis reaction was in the area of structure determination. In the days before the advent of spectroscopic techniques (Chapters 13-15), the structure of an unknown organic compound was determined by submitting it to a host of reactions. Often, a complex molecule was broken into several fragments to simplify the structural problem. After the individual fragments were identified, the original molecule could be mentally reconstructed from them. Alkenes were often cleaved to aldehydes and ketones by reaction with ozone. 

Under somewhat milder conditions (200°C), the reaction does not proceed as far as removing the functional groups, and the result is merely the hydrogenation of multiple bonds [38,39]. This is an efficient means of structure elucidation, especially when combined with ozonolysis [40,41 ] to establish the locations of multiple bonds in the molecule. In ozonolysis the substance supposed to contain a double bond is dissolved in CS2, ozonized at about —70°C and the ozonide is reduced with triphenylphosphine to produce aldehydes and/or ketones characteristic of the moieties linked by the double bond. 

Like permanganate, ozone cleaves double bonds to give ketones and aldehydes. However, ozonolysis is milder, and both ketones and aldehydes can be recovered without further oxidation. 

Bailey and Colomb278 described an ozonolysis of 2,5-diphenylfuran in methanol-acetone, with two equivalents of ozone, which gave 14% phenylglyoxal and 81% benzoic acid. Abnormal ozonizations such as this can be explained if we consider that the initial step is the normal 2,5-addition of ozone on the furan ring. Then 26 or the primary ozonides 27 or 28 could give the resulting ketonic product ... 

Ozonolysis of Tetramethylene and cis-3,4-Dimethyl- 3 -hexene. A solution of tetramethylethylene (0.503 gram, 5.98 mmoles) and cis-3,4-dimethyl-3-hexene (0.692 gram, 6.17 mmoles) in 20 ml pentane was ozonized to 63% theoretical yield at —40°C. The product mixture was analyzed by GPC using an 8-ft 10% XF-1150 column at 85°C and a flow rate of 150 ml/minute. The mixture contained 25 mg acetone diperoxide, 36.7 mg l,l,4-trimethyl-4-ethyl-2,3,5,6-tetraoxacyclohexane, and 23.2 mg methyl ethyl ketone diperoxide as determined by GPC using an internal standard. Total yield of diperoxides was 14%. The diperoxides were identified by comparing mp, infrared, NMR, and GPC data with those of authentic samples. 

Ozonolysis of cis-3,4-Dimethyl-3 -hexene. A solution of cis-3,4-di-methyl-3-hexene (98% pure, Chemical Samples Co.) (1.12 grams, 10 mmoles) in 50 ml pentane was ozonized at — 62°C until the blue color of excess ozone was evident. A nitrogen stream was used to purge the solution of excess ozone. Pentane was then carefully distilled off at atmospheric pressure. A water aspirator (20 mm Hg) was then used to remove the ketone product. Treatment of this material with 10 ml of an 0.1 M solution of 2,4-dinitrophenylhydrazine gave 2.33 grams of crude 2,4-dinitrophenylhydrazone. The crude product was recrystallized and identified as the 2,4-dinitrophenylhydrazone of methyl ethyl ketone, mp 115-116°C. Yield of the ketone was 92% based on olefin used. 

Ozonolysis of the s-alkylmercuric halides and the di-s-alkylmercurials produced the coresponding ketone. Although some carbon-carbon cleavage occurred, it was generally less than with the reaction of the primary organomercurials (see Reactions 13 and 14, Table I). In partial contrast to the results of Bockemuller and Pfeuffer (Reaction II), the ozonation of diisopropylmercury yielded acetic acid in addition to acetone (Reaction 14, Table I). 

Ozone, while somewhat inconvenient to use, is way qiecific in its reactions with alkenes. It is widely employed for selective synthesis, for qualitative and quantitative analysis of unsaturated compounds, and for studying the position of double bonds in macromolecules. The nature of the products obtained from ozonolysis reactions is determitted by the way in which the reaction is carried out Different workup procedures (hydrolytic, reductive or oxidative) can be used to produce alcohols, aldehydes, ketones, carboxylic acids or esters. 

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